Inhibition of noradrenergic signaling in rodent orbitofrontal cortex impairs the updating of goal-directed actions

  1. Juan Carlos Cerpa
  2. Alessandro Piccin
  3. Margot Dehove
  4. Marina Lavigne
  5. Eric J Kremer
  6. Mathieu Wolff
  7. Shauna L Parkes  Is a corresponding author
  8. Etienne Coutureau  Is a corresponding author
  1. CNRS, University of Bordeaux, France
  2. CNRS, University of Montpellier, France

Abstract

In a constantly changing environment, organisms must track the current relationship between actions and their specific consequences and use this information to guide decision-making. Such goal-directed behavior relies on circuits involving cortical and subcortical structures. Notably, a functional heterogeneity exists within the medial prefrontal, insular, and orbitofrontal cortices (OFC) in rodents. The role of the latter in goal-directed behavior has been debated, but recent data indicate that the ventral and lateral subregions of the OFC are needed to integrate changes in the relationships between actions and their outcomes. Neuromodulatory agents are also crucial components of prefrontal functions and behavioral flexibility might depend upon the noradrenergic modulation of the prefrontal cortex. Therefore, we assessed whether noradrenergic innervation of the OFC plays a role in updating action-outcome relationships in male rats. We used an identity-based reversal task and found that depletion or chemogenetic silencing of noradrenergic inputs within the OFC rendered rats unable to associate new outcomes with previously acquired actions. Silencing of noradrenergic inputs in the prelimbic cortex or depletion of dopaminergic inputs in the OFC did not reproduce this deficit. Together, our results suggest that noradrenergic projections to the OFC are required to update goal-directed actions.

Data availability

All data generated or analysed during this study are included in the supporting file

Article and author information

Author details

  1. Juan Carlos Cerpa

    CNRS, University of Bordeaux, Bordeaux, France
    Competing interests
    No competing interests declared.
  2. Alessandro Piccin

    CNRS, University of Bordeaux, Bordeaux, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9566-3808
  3. Margot Dehove

    CNRS, University of Bordeaux, Bordeaux, France
    Competing interests
    No competing interests declared.
  4. Marina Lavigne

    Institut de Génétique Moléculaire de Montpellier, CNRS, University of Montpellier, Montpellier, France
    Competing interests
    No competing interests declared.
  5. Eric J Kremer

    Institut de Génétique Moléculaire de Montpellier, CNRS, University of Montpellier, Montpellier, France
    Competing interests
    No competing interests declared.
  6. Mathieu Wolff

    CNRS, University of Bordeaux, Bordeaux, France
    Competing interests
    Mathieu Wolff, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3037-3038
  7. Shauna L Parkes

    CNRS, University of Bordeaux, Bordeaux, France
    For correspondence
    shauna.parkes@u-bordeaux.fr
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7725-8083
  8. Etienne Coutureau

    CNRS, University of Bordeaux, Bordeaux, France
    For correspondence
    etienne.coutureau@u-bordeaux.fr
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6695-020X

Funding

Agence Nationale de la Recherche (CE37-0019 NORAD)

  • Eric J Kremer
  • Etienne Coutureau

Fondation pour la Recherche Médicale (ECO20160736024)

  • Juan Carlos Cerpa

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Laura A Bradfield, University of Technology Sydney, Australia

Ethics

Animal experimentation: Experiments were performed in accordance with current French (Council directive 2013-118, February 1, 2013) and European (directive 2010-63, September 22, 2010, European Community) laws and policies regarding animal experimentation. The experiments received approval from the local Bordeaux Ethics Committee (CE50).

Version history

  1. Preprint posted: July 1, 2022 (view preprint)
  2. Received: July 5, 2022
  3. Accepted: February 17, 2023
  4. Accepted Manuscript published: February 20, 2023 (version 1)
  5. Version of Record published: March 6, 2023 (version 2)

Copyright

© 2023, Cerpa et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,017
    views
  • 249
    downloads
  • 3
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Juan Carlos Cerpa
  2. Alessandro Piccin
  3. Margot Dehove
  4. Marina Lavigne
  5. Eric J Kremer
  6. Mathieu Wolff
  7. Shauna L Parkes
  8. Etienne Coutureau
(2023)
Inhibition of noradrenergic signaling in rodent orbitofrontal cortex impairs the updating of goal-directed actions
eLife 12:e81623.
https://doi.org/10.7554/eLife.81623

Share this article

https://doi.org/10.7554/eLife.81623

Further reading

    1. Neuroscience
    Songyao Zhang, Tuo Zhang ... Tianming Liu
    Research Article

    Cortical folding is an important feature of primate brains that plays a crucial role in various cognitive and behavioral processes. Extensive research has revealed both similarities and differences in folding morphology and brain function among primates including macaque and human. The folding morphology is the basis of brain function, making cross-species studies on folding morphology important for understanding brain function and species evolution. However, prior studies on cross-species folding morphology mainly focused on partial regions of the cortex instead of the entire brain. Previously, our research defined a whole-brain landmark based on folding morphology: the gyral peak. It was found to exist stably across individuals and ages in both human and macaque brains. Shared and unique gyral peaks in human and macaque are identified in this study, and their similarities and differences in spatial distribution, anatomical morphology, and functional connectivity were also dicussed.

    1. Neuroscience
    Avani Koparkar, Timothy L Warren ... Lena Veit
    Research Article

    Complex skills like speech and dance are composed of ordered sequences of simpler elements, but the neuronal basis for the syntactic ordering of actions is poorly understood. Birdsong is a learned vocal behavior composed of syntactically ordered syllables, controlled in part by the songbird premotor nucleus HVC (proper name). Here, we test whether one of HVC’s recurrent inputs, mMAN (medial magnocellular nucleus of the anterior nidopallium), contributes to sequencing in adult male Bengalese finches (Lonchura striata domestica). Bengalese finch song includes several patterns: (1) chunks, comprising stereotyped syllable sequences; (2) branch points, where a given syllable can be followed probabilistically by multiple syllables; and (3) repeat phrases, where individual syllables are repeated variable numbers of times. We found that following bilateral lesions of mMAN, acoustic structure of syllables remained largely intact, but sequencing became more variable, as evidenced by ‘breaks’ in previously stereotyped chunks, increased uncertainty at branch points, and increased variability in repeat numbers. Our results show that mMAN contributes to the variable sequencing of vocal elements in Bengalese finch song and demonstrate the influence of recurrent projections to HVC. Furthermore, they highlight the utility of species with complex syntax in investigating neuronal control of ordered sequences.